Abstract
Nootkatone (NK), a sesquiterpene naturally derived from citrus species, was investigated for its protective effect against UVB-induced damage in HaCaT cells and its underlying mechanisms. NK effectively suppressed UVB-mediated cell death and significantly modulated expression of skin hydration genes; NK (100 μM) increased mRNA levels of collagen-1 and HAS by 44.6 and 34.7%, respectively, while downregulating HYAL by 46.8%. NK also reduced MMP1/2 expression, key matrix metalloproteinases, but enhanced mRNA levels of skin barrier factors, Filaggrin, Loricrin, and Involucrin by up to 45%. Additionally, NK lowered UVB-induced ROS production and elevated antioxidant levels (NRF2, HO-1, catalase, SOD1, and Gpx), and decrease the protein levels of xenobiotic factors, AhR and CYP1A1. These findings suggest that NK protects skin integrity against UVB-induced photoaging through the modulation of NRF2-HO-1 and AhR-CYP1A1 signaling pathways. NK shows promise as a functional agent, either edible or topical, for protecting against UVB-induced skin damage. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-024-01791-x.